This invention relates to the treatment of a mammal with severe blood loss or hemorrhagic shock and, more particularly to a pharmaceutical composition and method for the treatment of severe blood loss, and for the inhibition or treatment of hemorrhagic shock in a mammal.
Hemorrhagic shock is a life-threatening condition brought on by severe blood loss. For example, hemorrhagic shock may originate from internal or external hemorrhage, gun shot wounds, severe trauma or any other condition associated with blood loss. Unfortunately, because of the severity and complexity of hemorrhagic shock, a patient is likely to die unless treated during a relatively short treatment window, generally known as the "golden hour".
Hemorrhagic shock is an extremely complex process, stimulating multiple injury pathways. That is, the pathophysiology of hemorrhagic shock is multifactorial. For example, hemorrhagic shock stimulates the release of cytokines and nitric oxide, as well as the formation of peroxynitrite and the generation of superoxide radical. In addition, hemorrhagic shock stimulates pathways which release platelet activating factor, and induces alterations in the complement cascade and coagulation cascade. Furthermore, hemorrhagic shock stimulates neuroendocrine responses, electrolyte disturbances and metabolic changes. Accordingly, the treatment and management of a patient experiencing hemorrhagic shock is extremely complex.
The initial phase of hemorrhagic shock, unless rapidly corrected, is followed by progressive tissue ischemia, end-organ disfunction and refractory vascular failure. Hemorrhagic shock also is associated with early vasomotor paralysis and cardiovascular collapse. Accordingly, conventional resuscitation methods have been directed toward hemostasis and intravenous infusion of sufficiently large volumes of fluid, preferably blood, in order to restore cardiac index, improve oxygen-carrying capacity and minimize cellular hypoxia. Although this approach may be well suited for the in-patient setting, it is impractical in field situations where the supply of resuscitation fluid is limited. Therefore, it would be extremely beneficial to have a method for treating hemorrhagic shock which does not require large volumes of resuscitation fluid.
In addition, traditional resuscitation methods using pharmaceutical intervention usually involve a catecholamine, such as norepinephrine for example, which rapidly loses its effectiveness within one hour, and thus is of limited clinical utility. Accordingly, it would be extremely desirable to have a method and composition for treating hemorrhagic shock which does not lose its effectiveness in a short period of time.